Corneal ulceration and stromal degradation due to infection, vitamin A deficiency, chemical injury or autoimmune disease is the major cause of visual loss and blindness in the world. Proteases have been implicated in stromal degradation but only one enzyme, collagenase, has been extensively studied. We hypothesize that other proteases are also involved based on our preliminary data. The specific aims of the studies proposed herein are: (1) to determine the source, kinds and relative importance of various proteases and antiproteases involved in the initiation and the progression of the degradation process, (2) to determine biochemical differences in the proteins, glycoproteins and proteoglycans and in the antiproteases in the eyes of vitamin A deficient animals that might account for the rapid stromal degradation which occurs in keratomalacia, (3) to determine if protease inhibitors specific for those proteases which are shown to play major roles in the degradative process, can be used to reduce or prevent the degradation or scarring of the corneal stroma. Animal models for Pseudomonas keratitis, xerophthalmia and keratomalacia developed and studied extensively at the Medical College of Wisconsin by Drs. Diane (Van Horn) Hatchell, Starkey Davis and Robert Hyndiuk will be used. Proteases and inhibitors (and their levels) will be determined at various times after infection of normal and xerophthalmic corneas and their presence correlated with the clinical, histological and ultrastructural alterations in the corneal tissue. New histochemical techniques for localizing enzyme activity in tissue sections will be used in combination with standard techniques for enzyme and inhibitor assays, electrophoretic separation of tissue extract components, histology and electron microscopy. The results of these studies will lead to a better understanding of the mechanisms involved in stromal degradation, as well as to better methods of treatment of corneal ulceration processes.